NCT01363609

Effects of Glucagon Like Peptide-1(GLP-1) and Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes

Central Effects of Endogenous Glucagon Like Peptide-1 (GLP-1) and the GLP-1 Analog Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The aim of this study is to investigate if endogenous Glucagon Like Peptide -1 (GLP-1) has an effect on brain satiety and reward systems and if there are alterations in obese patients with type 2 diabetes (T2DM). Secondly, the aim is to investigate whether treatment with a GLP-1 analog, liraglutide, restores these signals in obese patients with type 2 diabetes. Finally, also the endogenous GLP-1 effects will be investigated in obese individuals before and after gastric bypass surgery on brain satiety and reward systems.

Detailed description

First aim will be addressed in a cross-sectional randomized study. 20 healthy, lean and 20 obese individuals with type 2 diabetes (T2DM) will be exposed to food cues and with concomitant infusion of glucagon Like peptide-1 (GLP-1) receptor antagonist or saline, to assess the involvement of endogenous GLP-1, secreted in response to a meal. Measurements activation of CNS circuits involved in satiety and reward will be performed using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The second aim will be addressed in cross-over randomized-controlled trial (RCT) in the T2DM patients only. Patients will be randomly assigned liraglutide vs insulin glargine treatment, during a treatment period of 12 weeks each with a 12-week washout period in between. The investigators will perform the same fMRI protocol. The third aim will be addressed in a study with obese individuals who are scheduled for a gastric bypass surgery. The same protocol as for the first aim will be performed and this will be before and after the surgery in the same individuals.

Conditions

• Obesity
• Type 2 Diabetes

Interventions

Type	Name	Description
DRUG	Liraglutide treatment 12 weeks	liraglutide will be started with a titration period of 2 weeks: week 1 0.6mg once daily, week 2 1.2mg once daily. If well tolerated, treatment will be continued for 10 more weeks in dosage of 1.8mg once daily
DRUG	insulin glargine treatment	Insulin glargine treatment consist a treatment period of 12 weeks. Treatment will start with a dosage of 10 IU once daily. Patient will self-titrate the insulin glargine dosage based on self-monitored fasting blood glucose (FBG) concentrations for the previous 3 days using the following guideline: If FBG levels are above 5.6 mmol/L (100-153 mg/dL) on 3 consecutive mornings, the daily dose is to be increased by 2 IU/day. If hypoglycemia documented by glucose concentration \< 3.3 mmol/L (60 mg/dL) or requiring assistance occurs without an easily identifiable reason (skipped meal, excessive physical activity), the daily dose is to be downregulated, with -2 IU/day
DRUG	GLP-1 receptor antagonist	Exendin 9-39 will be infused intravenously at doses of 600 pM/kg • min. This will only be during one of the visit for the healthy lean controls and the T2DM group, and during two visits in the group with obesity planned for gastric bypass surgery

Timeline

• Start date: 2011-10-01
• Primary completion: 2015-01-01
• Completion: 2015-01-01
• First posted: 2011-06-01
• Last updated: 2015-02-18

Locations

1 site across 1 country: Netherlands